This DN has recruited 8 Doctoral Candidates (DCs) who have undertaken a range of training activities. This has included research-focued training and includes consortium wide training, bespoke personalised training packages and operational training, entrepreneurial, management and presentations skills and ethics training. Their research is conducted across five research work packages:
WP1 Innovative CAR-/TCR-engineered T cell therapies
WP2 Innovative therapies to restore antigen specific tolerance
WP3 ADAMTS13 (targeted) clearance
WP4 Long-term follow-up of autoimmune diseases
WP5 Identify the most promising (combined) innovative therapies
Each of the DCs has an individual, personalised research project joint supervised by a multi-disciplinary cross-sector team of at least two supervisors. Each project has been designed to take full advantage of expertise, methodology and technology available within the consortium.
DC1 gathered iTTP patient data, focusing on patients who had been treated with innovative agents like obinutuzumab and daratumumab. After compiling the data and conducting statistical analyses their findings were published. DC2 and DC3 have successfully developed innovative CAR T cells, TMs, and target cells for CAR T cell therapy and have proven their efficacy in in vitro cytotoxicity assays. DC4 isolated Peripheral Blood Mononuclear Cells (PBMCs) and sorted T CD4+ cells using FACS from healthy donors to next stimulate PBMCs with ADAMTS13-derived peptides and identify a T-cell receptor (TCR). DC5 has been constructing tolerogenic vaccines by generating fusion proteins of ADAMTS13 with relevant proteins, aiming to create tolerogenic vaccines. Additionally, DC5 selected an ADAMTS13 CUB2 domain-derived peptide, and coupled it with the TAT cell-penetrating peptide to target red blood cells (RBCs) and harness their tolerogenic properties. DC6 successfully designed and scaled up the manufacturing of PS-liposomes encapsulating a single ADAMTS13-derived peptide. DC7 made progressed in understanding the cell types and receptors involved in the clearance of ADAMTS13. Furthermore, DC7 identified a new role for a specific receptor in regulating the physiological clearance of ADAMTS13 in vivo. DC8 isolated and cryopreserved PBMCs from iTTP patients, including those with relapses and those in remission, and sent the samples to DC5 and DC6. Additionally, a database was established at SMW, according to the standardized follow-up protocol set up in Paris, to track iTTP patients with index events and available samples prior to these events. Finally, with the collective efforts of all DCs and close collaboration, standardized clinical databases for TTP and ADAMTS13 measurements were established during their 5-week clinical training in Paris, marking a significant milestone in the field.
